The present invention relates generally to the preservation of pharmaceutical compositions. In particular, the present invention relates to the use of anionic surfactants, particularly amino acid based surfactants, to prevent or to reduce binding of the antimicrobial components of topically administrable pharmaceutical compositions to other components contained therein, thereby improving the antimicrobial efficacy of such compositions.
In recent years, a number of ophthalmic compositions have been introduced that contain a variety of components, such as carboxyvinyl polymers (e.g., Carbopol.RTM.), ion exchange resins (e.g., Amberlite.RTM.), or other large polyelectrolytes, which provide sustained release of the ophthalmic agent(s), as well as increased patient comfort. Such compositions are described, for example, in U.S. Pat. No. 4,911,920 (Jani et al.). Although these compositions are comfortable and have sustained release characteristics, cationic antimicrobials, such as benzalkonium chloride (BAC), which are often added as preservatives to such compositions, tend to bind to the anionic polyelectrolytes present in the formulations, resulting in loss of antimicrobial effectiveness.
Sarcosinate surfactants are composed of acylated sarcosines. Sarcosine (CH.sub.3 --NH--CH.sub.2 --COOH), an amino acid normally found in starfish and sea urchins, is chemically related to glycine (NH.sub.2 --CH.sub.2 --COOH), a basic amino acid in mammals. Common fatty acids and their derivatives utilized in the manufacture of sarcosinate surfactants are lauric, oleic, and myristic acids and their esters and halides. Because of their mildness, sarcosinate surfactants have been utilized in shampoos, mouthwashes, skin cleansers, sunscreens, aerosol shaving lathers and other personal care products. To date, the main applications of these types of surfactants have been in the cosmetic industry. For example, European Patent Application No. 0 194 097 (Schmidt et al.), assigned to Procter & Gamble, mentions sodium lauroyl sarcosinate as the mild anionic surfactant utilized in an aerosol skin-cleansing and moisturizer mousse.
U.S. Pat. No. 5,520,920 (Castillo, et al.) discloses the use of certain modified sarcosinates and lactylates to enhance antimicrobial effectiveness of ophthalmic compositions, particularly in the case where cationic preservatives otherwise bind to anionic polyelectrolytes. The modified sarcosinates have the formula: ##STR1## wherein: R.sup.1 =C.sub.4 -C.sub.27 saturated or unsaturated hydrocarbon; M=H or a pharmaceutically acceptable salt; and
n=1, 2 or 3. PA1 M.sup.+=H or a pharmaceutically acceptable salt.
Representative modified sarcosinates include those sold under the Hamposyl.RTM. trade name, such as lauroyl sarcosine (Hamposyl.RTM. L), oleoyl sarcosine (Hamposyl.RTM. O), myristoyl sarcosine (Hamposyl.RTM. M), cocoyl sarcosine (Hamposyl.RTM. C), stearoyl sarcosine (Hamposyl.RTM. S), and pelargodoyl sarcosine (Hamposyl.RTM. P). Representative lactylates include sodium capryl lactylate (Pationic.RTM. 122A).
Additional solutions to the problem of cationic preservative--anionic polyelectrolyte binding problem in topically administrable pharmaceutical compositions are desirable.
Anionic amino acid surfactants other than the Hamposyl.RTM. surfactants are known and include, for example, those surfactants sold under the Amilite.TM. and Amisoft.TM. trade names (Ajinomoto Co., Inc., Tokyo, Japan). According to its product brochure, one such surfactant, Amilite.TM. GCK-12, is used as a detergent, a foaming agent, an emulsifier, a solubilizer and a dispersing agent. Examples of applications of Amilite.TM. GCK-12 include cosmetics and toiletries (hair shampoo and body wash), face wash (facial washing foam, facial washing creme, facial washing liquid and make-up remover), facial soap, toothpaste, bath soap, contact lens cleaners and household cleaners. Amisoft.TM. surfactants are described as gentle cleansers for the skin and hair. Major applications of Amisoft.TM. surfactants include facial and body cleansers, hair shampoos, syndet bars, body care and dermatological products.